Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CELL–CELL JUNCTIONS
1049
microvilli
intestinal lumen
cell 1 cell 2
focal
connection
focal
connection
tight
junction
plasma
membrane
(A)
(B)
ridges of transmembrane
particles forming sealing
strands (P face)
lateral plasma
membrane
0.5 µm
(C)
50 nm
Figure 19–20 The structure of a tight junction between epithelial cells of the small intestine. The junctions are shown
(A) schematically, (B) in a freeze-fracture electron micrograph, and (C) in a conventional electron micrograph. In (B), the plane of
the micrograph is parallel to the plane of the membrane, and the tight junction appears as a band of branching sealing strands
that encircle each cell in the epithelium (see Figure 19–21A). In (C), the junction is seen in cross section as a series of focal
connections between the outer leaflets of the two interacting plasma membranes, each connection corresponding to a sealing
strand in cross section. (B and C, from N.B. Gilula, in Cell Communication [R.P. Cox, ed.], pp. 1–29. New York: Wiley, 1974.)
MBoC6 m19.25/19.20
will form tight-junctional connections with one another. Normal tight junctions
also contain a second major transmembrane protein called occludin, which is not
essential for the assembly or structure of the tight junction but is important for
limiting junctional permeability. A third transmembrane protein, tricellulin, is
required to seal cell membranes together and prevent transepithelial leakage at
the points where three cells meet.
The claudin protein family has many members (24 in humans), and these are
expressed in different combinations in different epithelia to confer particular permeability
properties on the epithelial sheet. They are thought to form paracellular
pores—selective channels allowing specific ions to cross the tight-junctional barrier,
from one extracellular space to another. A specific claudin found in kidney
epithelial cells, for example, is needed to let Mg 2+ pass between the cells of the
kidney tubules so that this ion can be resorbed from the urine into the blood. A
mutation in the gene encoding this claudin results in excessive loss of Mg 2+ in the
urine.
Scaffold Proteins Organize Junctional Protein Complexes
Like the cadherin molecules of an adherens junction, the claudins and occludins
of a tight junction interact with each other on their extracellular sides to promote
junction assembly. Also as in adherens junctions, the organization of adhesion
proteins in a tight junction depends on additional proteins that bind the cytoplasmic
side of the adhesion proteins. The key organizational proteins at tight junctions
are the zonula occludens (ZO) proteins. The three major members of the ZO
family—ZO-1, ZO-2, and ZO-3—are large scaffold proteins that provide a structural
support on which the tight junction is built. These intracellular molecules